Annals of Vascular Surgery

, Volume 10, Issue 3, pp 244–253 | Cite as

Local application of vancomycin for prophylaxis of graft infection: Release of vancomycin from antibiotic-bonded dacron grafts, toxicity in endothelial cell culture, and efficacy against graft infection in an animal model

  • Elke Muhl
  • Sören Gatermann
  • Hans Iven
  • Andreas Dendorfer
  • Hans-Peter Bruch
Original Articles


Methicillin-resistant strains ofStaphylococcus epidermidis cause an increasing number of prosthetic infections. This prompted us to test the uptake of vancomycin in various graft materials in vitro, its influence on graft healing, and its efficacy against graft infection in pigs. Incubation of six different Dacron graft materials in a vancomycin solution (20 gm/L) was performed. Grafts were then placed in plasma, and samples were taken over 72 hours to determine vancomycin levels. Release of vancomycin ranged from 775 µg/cm2 to 3691 µg/cm2 after 1 hour of incubation. Gelatin-covered grafts increased release of vancomycin fourfold when incubation time was extended to 24 hours; uncovered grafts or the collagen-covered graft did not. Graft healing was not complicated when a vancomycin-bonded, gelatin-impregnated Dacron graft was implanted to replace the common femoral artery in pigs. Four weeks after implantation, histologic examination revealed normal development of neointima and perigraft scar tissue in the vancomycin-treated (n=4) and untreated (n=5) grafts. To test the efficacy of local vancomycin against graft infection, grafts were implanted in the groin of pigs and contaminated with 2 × 107 colony-forming units ofStaphylococcus aureus. Four weeks after implantation, all grafts were infected in the untreated group (n=6), with abscess, nonincorporated graft, and detection ofS. aureus from the graft. In the treatment group (n=6) vancomycin was added to the contaminated grafts. As a carrier for the vancomycin, we used a resorbable gelatin-glycerol foam. All grafts healed without infection. The difference between the treated and untreated groups is statistically significant (p<0.05). We conclude that it may be effective to prevent graft infection with local application of vancomycin if an in situ replacement of infected graft (infected by gram-positive bacteria) is necessary or if there is a high risk of infection by methicillin-resistant staphylococci.


Vancomycin Femoral Artery Scar Tissue Untreated Group Local Application 
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  1. 1.
    Kaiser AB, Clayson KR, Mulherin JL, et al. Antibiotic prophylaxis in vascular surgery. Ann Surg 1978;188:283–289.PubMedGoogle Scholar
  2. 2.
    Pitt HA, Postier RG, McGowan WAL, et al. Prophylactic antibiotics in vascular surgery: Topical, systemic or both? Ann Surg 1980;192:356–364.PubMedCrossRefGoogle Scholar
  3. 3.
    Salzmann G. Perioperative infection prophylaxis in vascular surgery: A randomized prospective study. J Thorac Cardiovasc Surg 1983;31:239–242.Google Scholar
  4. 4.
    Hasselgren PO, Ivarsson L, Risberg B, et al. Effects of prophylactic antibiotics in vascular surgery: A prospective, randomized, double-blind study. Ann Surg 1984;200:86–92.PubMedCrossRefGoogle Scholar
  5. 5.
    Jensen LJ, Aagaard MT, Schifter S. Prophylactic vancomycin versus placebo in arterial prosthetic reconstructions. J Thorac Cardiovasc Surg 1985;33:300–303.Google Scholar
  6. 6.
    Dale WJA. Management of vascular surgical problems. London: McGraw-Hill, 1986, pp 366–380.Google Scholar
  7. 7.
    Worning AM, Frimodt-Möller N, Ostri P, et al. Antibiotic prophylaxis in vascular reconstructive surgery: A double-blind placebo-controlled study. J Antimicrob Chemother 1986;17:105–109.PubMedCrossRefGoogle Scholar
  8. 8.
    Szilagyi DE, Smith RF, Elliott JP, et al. Infection in arterial reconstruction with synthetic grafts. Ann Surg 1972;176:321–333.PubMedCrossRefGoogle Scholar
  9. 9.
    Goldstone J, Moore WS. Infection in vascular prostheses: Clinical manifestations and surgical management. Am J Surg 1974;128:225–232.CrossRefPubMedGoogle Scholar
  10. 10.
    Sandmann W, Gisbertz KH, Kovacicek S. Die wundinfektion nach arterienoperationen im becken-bein-bereich. Chirurg 1976;47:130–139.PubMedGoogle Scholar
  11. 11.
    Ernst CB, Campbell HC, Daugherty ME, et al. Incidence and significance of intraoperative bacterial cultures during abdominal aortic aneurysmectomy. Ann Surg 1977;185:626–630.PubMedCrossRefGoogle Scholar
  12. 12.
    Liekweg WG, Greenfield LJ. Vascular prosthetic infections: Collected experience and results of treatment. Surgery 1977;81:335–342.PubMedGoogle Scholar
  13. 13.
    Scobie TK, Elder RH, McPhail N. Infected abdominal aortic grafts. Can J Surg 1978;21:527–531.PubMedGoogle Scholar
  14. 14.
    Landreneau MD, Raju S. Infections after elective bypass surgery for lower limb ischemia: The influence of preoperative transcutaneous arteriography. Surgery 1981;90:956–961.PubMedGoogle Scholar
  15. 15.
    Fleischer GM, Heinrich P. Probleme der infektion bei gefäss-operationen. Zentralbl Chir 1982;107:664–667.PubMedGoogle Scholar
  16. 16.
    Bunt TJ, Haynes JL. Synthetic vascular graft infection: The continuing headache. Am Surg 1984;50:43–48.PubMedGoogle Scholar
  17. 17.
    Macbeth GA, Rubin JR, McIntyre KE, et al. The relevance of arterial wall microbiology to the treatment of prosthetic graft infections: Graft infection vs. arterial infection. J Vasc Surg 1984;1:750–756.CrossRefPubMedGoogle Scholar
  18. 18.
    Bandyk DF, Berni GA, Thiele BL, et al. Aortofemoral graft infection due toStaphylococcus epidermidis. Arch Surg 1984;119:102–108.PubMedGoogle Scholar
  19. 19.
    Lorentzen JE, Nielsen OM, Arendrup H, et al. Vascular graft infection: An analysis of sixty-two graft infections in 2411 consecutively implanted synthetic vascular grafts. Surgery 1985;98:81–86.PubMedGoogle Scholar
  20. 20.
    Jensen LJ, Kimose HH. Prosthetic graft infections: A review of 720 arterial prosthetic reconstructions. J Thorac Cardiovasc Surg 1985;33:389–391.CrossRefGoogle Scholar
  21. 21.
    Edwards WH Jr, Martin RS, Jenkins JM, et al. Primary graft infections. J Vasc Surg 1987;6:235–239.CrossRefPubMedGoogle Scholar
  22. 22.
    Kaebnick HW, Bandyk DF, Bergamini TW, et al. The microbiology of explanted vascular prostheses. Surgery 1987;102:756–762.PubMedGoogle Scholar
  23. 23.
    Durham JR, Malone JM, Bernhard VM. The impact of multiple operations on the importance of arterial wall cultures. J Vasc Surg 1987;5:160–169.CrossRefPubMedGoogle Scholar
  24. 24.
    Zühlke HV. Septische gefässchirurgie/zühlke harnoss. Vienna: Ueberreuter-Wissenschafts-Verlag, 1988, pp 1–406.Google Scholar
  25. 25.
    Brook I. Role of anaerobic bacteria in aortofemoral graft infection. Surgery 1988;104:843–845.PubMedGoogle Scholar
  26. 26.
    Samson RH, Veith FJ, Janko GS, et al. A modified classification and approach to the management of infections involving peripheral arterial prosthetic grafts. J Vasc Surg 1988;8:147–153.CrossRefPubMedGoogle Scholar
  27. 27.
    Calligaro KD, Veith FJ, Gupta SK, et al. A modified method for management of prosthetic graft infection involving an anastomosis to the common femoral artery. J Vasc Surg 1990;11:485–492.CrossRefPubMedGoogle Scholar
  28. 28.
    Parson CL, Stein PC, Dobke MK, et al. Diagnosis and therapy of subclinically infected prostheses. Surg Gynecol Obstet 1993;177:504–506.PubMedGoogle Scholar
  29. 29.
    Voss A. Staphylokokken-wirksame antibiotika: Klinische bedeutung und ihre anwendung. In Daschner F, ed. Staphylokokken im Krankenhaus. Frankfurt: Universimed Verlag, 1992, pp 24–31.Google Scholar
  30. 30.
    Sugarman B. In vitro adherence of bacteria to prosthetic vascular grafts. Infection 1982;10:9–12.CrossRefPubMedGoogle Scholar
  31. 31.
    Jaffe EA, Nachman RL, Becker CG, et al. Culture of human endothelial cells derived from umbilical veins: Identification by morphologic and immunologic criteria. J Clin Invest 1973;52:2745–2756.PubMedCrossRefGoogle Scholar
  32. 32.
    Péchère JC. Which antibiotic to bind to a vascular prosthesis? [abst]. Presented at the Second International Conference on the Prevention of Infection. Nice, France: May 4–5, 1992.Google Scholar
  33. 33.
    Simon C, Stille W. Antibiotikatherapie in klinik und praxis. Stuttgart: Schattauer, 1989, pp 390–393.Google Scholar
  34. 34.
    Maki DG, Bohn MJ, Stolz SM, et al. Comparative study of cefazolin, cefamandole, and vancomycin for surgical prophylaxis in cardiac and vascular operations: A double-blind randomized trial. J Thorac Cardiovasc Surg 1992;104:1423–1434.PubMedGoogle Scholar
  35. 35.
    Goëau-Brissonnière O, Leport C, Bacourt F, et al. Prevention of vascular graft infection by rifampin bonding to a gelatinsealed Dacron graft. Ann Vasc Surg 1991;5:408–412.PubMedCrossRefGoogle Scholar
  36. 36.
    Goëau-Brissonnière O, Leport C, Bacourt F, et al. Prevention of vascular graft infections by rifampin bonding to a gelatinsealed Dacron graft [abst]. Presented at the Second International Conference on the Prevention of Infection. Nice, France: May 4–5, 1992.Google Scholar
  37. 37.
    Strachan CJL, Newsom SWB, Ashton TR. The clinical use of an antibiotic-bonded graft [abstract]. Presented at the Second International Conference on the Prevention of Infection. Nice, France: May 4–5, 1992.Google Scholar
  38. 38.
    Strachan CJL, Newsom SWB, Ashton TR. The clinical use of an antibiotic-bonded graft. Eur J Vasc Surg 1991;5:627–632.CrossRefPubMedGoogle Scholar
  39. 39.
    Avramovic JR, Fletcher JP. Rifampicin impregnation of a protein-sealed Dacron graft: An infection-resistant prosthetic vascular graft. Aust NZ J Surg 1991;61:435–440.CrossRefGoogle Scholar
  40. 40.
    McDougal EG, Burnham S, Johnson G. Rifampin protection against experimental graft sepsis. J Vasc Surg 1986;4:5–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Powell TW, Burnham S, Johnson G. A passive system using rifampin to create an infection-resistant vascular prosthesis. Surgery 1983;94:765–769.PubMedGoogle Scholar
  42. 42.
    Ashton TR, Cunningham JD, Paton D, et al. Antibiotic loading of vascular grafts [abst]. Proc Soc Biomater 1990;13:235.Google Scholar
  43. 43.
    Wakefield TW, Schaberg DR, Pierson CL, et al. Treatment of established prosthetic vascular infection with antibiotics preferentially concentrated in leukocytes. Surgery 1987;102:8–14.PubMedGoogle Scholar
  44. 44.
    Rutledge R, Baker VV, Sherertz R, et al. Rifampin and cefazolin as prophylactic agents: A comparison in an animal model of vascular graft infection. Arch Surg 1982;117:1164–1165.PubMedGoogle Scholar
  45. 45.
    Hake U, Gabbert H, Iversen S, et al. Evaluation of healing of precoated vascular Dacron prostheses. Langenbecks Arch Chir 1991;376:323–329.CrossRefPubMedGoogle Scholar
  46. 46.
    Dinnendahl V, Fricke U. Arzneistoff-profile. Frankfurt: GOVI-Verlag, 1990.Google Scholar
  47. 47.
    Birinyi LK, Douville EC, Lewis SA, et al. Increased resistance to bacteremic graft infection after endothelial cell seeding. J Vasc Surg 1987;5:193–197.CrossRefPubMedGoogle Scholar
  48. 48.
    Rosenman JE, Kempczinski RF, Berlatzky Y, et al. Bacterial adherence to endothelial-seeded polytetrafluoroethylene grafts. Surgery 1985;98:816–823.PubMedGoogle Scholar
  49. 49.
    Clagett GP, Burkel WE, Sharefkin JB, et al. Antithrombotic character of canine endothelial cell-seeded arterial prostheses. Surg Forum 1984;33:471–473.Google Scholar
  50. 50.
    Oertenwall P. Endothelial cell seeding: Effects on vascular graft thrombogenicity. Thesis. Göteborg, Sweden: University of Göteborg, 1989.Google Scholar
  51. 51.
    Sharefkin JB, Latker C, Smith M, et al. Early normalization of platelet survival by endothelial seeding of Dacron arterial prostheses in dogs. Surgery 1982;92:385–393.PubMedGoogle Scholar
  52. 52.
    Brigham KL, Meyrick B, Berry LC, et al. Antioxidants protect cultured bovine lung endothelial cells from injury by endotoxins. J Appl Physiol 1987;63:840–850.PubMedGoogle Scholar
  53. 53.
    Denecke SM, Steiger V, Fanburg BL. Effect of hyperoxia on glutathione levels and glutamic acid uptake in endothelial cells. J Appl Physiol 1987;63:1966–1971.PubMedGoogle Scholar
  54. 54.
    Freeman BA, Young SL, Crapo JD. Liposome-mediated augmentation of superoxide dismutase in endothelial cells prevents oxygen injury. J Biol Chem 1983;258:12534–12542.PubMedGoogle Scholar
  55. 55.
    Sauvage LE, Berger KE, Wood SJ, et al. Interspecies healing of porous arterial prostheses. Arch Surg 1974;109:698–705.PubMedGoogle Scholar
  56. 56.
    Wesolow A. The healing of arterial prostheses: The state of the art. Thorac Cardiovasc Surg 1982;30:196–208.PubMedCrossRefGoogle Scholar
  57. 57.
    Wesolowski SA, Fries ChC, Karlson KE, et al. Porosity: Primary determinant of ultimate fate of synthetic vascular grafts. Surgery 1961;50:91–96.PubMedGoogle Scholar
  58. 58.
    Salm TJV, Okike ON, Pasque MK, et al. Reduction of sternal infection by application of topical vancomycin. J Thorac Cardiovasc Surg 1989;98:618–622.PubMedGoogle Scholar
  59. 59.
    Scott DM, Rotschafer JC, Behrens F. Use of vancomycin and tobramycin polymethylmethacrylate impregnated beads in the management of chronic osteomyelitis. Drug Intell Clin Pharm 1988;22:480–483.PubMedGoogle Scholar
  60. 60.
    Gerhart TN, Roux RD, Horowitz G, et al. Antibiotic release from an experimental biodegradable bone cement. J Orthop Res 1988;6:585–592.CrossRefPubMedGoogle Scholar

Copyright information

© Annals of Vascular Surgery Inc. 1996

Authors and Affiliations

  • Elke Muhl
    • 1
  • Sören Gatermann
    • 1
  • Hans Iven
    • 1
  • Andreas Dendorfer
    • 1
  • Hans-Peter Bruch
    • 1
  1. 1.From the Department of Surgery, Microbiology, and PharmacologyUniversity of LuebeckLuebeckGermany

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